Cao Xianyong, He Lin, Li Yanhua
Department of Ophthalmology, The Third Affiliated Hospital of Xinxiang Medical University, Eye Hospital of Xinxiang Medical University Xinxiang 453000, Henan Province, China.
Int J Clin Exp Pathol. 2015 Oct 1;8(10):12549-56. eCollection 2015.
The aim of the study was to evaluate the antitumor effects of the PPARγ agonist rosiglitazone on the human retinoblastoma. The cell biological behavior was detected, specifically, the effects of rosiglitazone on cell viability and apoptosis of the human retinoblastoma Y79 cells were investigated by MTT assay and Hochest 33258 staining and the migration assay showed that rosiglitazone blocked the invasion and migration of the carcinoma cells through the reconstituted extracellular matrix (Matrigel). The effect of rosiglitazone on NF-κB-dependent reporter gene transcription induced by LPS was analyzed by NF-κB-luciferase assay. Then human retinoblastoma Y79 cells were subcutaneously transplanted in BALB/c nude mice, and the animals were treated with rosiglitazone (20 mg/kg, 40 mg/kg, and 80 mg/kg) to verify its anti-tumor effect in vivo. Rosiglitazone suppressed the viability of Y79 cells dose- and time-dependently and induced apoptosis in Y79 cells in vitro. Molecular biology analysis found that rosiglitazone could modulate the proliferative and apoptosis related signal, reduce NF-κB-dependent reporter gene transcription induced by LPS. Rosiglitazone markedly reduced the growth of Y79 cells transplanted into the mice without causing significant side effects. Our results suggested that rosiglitazone demonstrated antitumor activity against the human retinoblastoma Y79 cells by inhibiting cell growth, inducing apoptosis and inhibiting metastasis and invasion in vitro and delaying tumor growth in vivo.
本研究的目的是评估过氧化物酶体增殖物激活受体γ(PPARγ)激动剂罗格列酮对人视网膜母细胞瘤的抗肿瘤作用。检测细胞生物学行为,具体而言,通过MTT法和Hochest 33258染色研究罗格列酮对人视网膜母细胞瘤Y79细胞活力和凋亡的影响,迁移实验表明罗格列酮通过重组细胞外基质(基质胶)阻断癌细胞的侵袭和迁移。通过NF-κB荧光素酶测定分析罗格列酮对脂多糖(LPS)诱导的NF-κB依赖的报告基因转录的影响。然后将人视网膜母细胞瘤Y79细胞皮下移植到BALB/c裸鼠体内,并用罗格列酮(20mg/kg、40mg/kg和80mg/kg)处理动物以验证其体内抗肿瘤作用。罗格列酮在体外剂量和时间依赖性地抑制Y79细胞的活力并诱导Y79细胞凋亡。分子生物学分析发现罗格列酮可调节增殖和凋亡相关信号,降低LPS诱导的NF-κB依赖的报告基因转录。罗格列酮显著降低移植到小鼠体内的Y79细胞的生长,且未引起明显的副作用。我们的结果表明,罗格列酮通过在体外抑制细胞生长、诱导凋亡、抑制转移和侵袭以及在体内延缓肿瘤生长,对人视网膜母细胞瘤Y79细胞显示出抗肿瘤活性。